Teicoplanin dosing strategy for treatment of Staphylococcus aureus in Korean patients with neutropenic fever

Purpose

The present study was conducted to determine and compare the target attainment rate (TAR) between microorganism-nonspecific (C_trough) and microorganism-specific (AUC₂₄/MIC) targets over two weeks of teicoplanin administration according to several dose regimens for the treatment of Staphylococcus aureus in Korean patients with neutropenic fever.

Materials and Methods

One thousand virtual concentrations were obtained for each dose using the population pharmacokinetic parameters of teicoplanin adopted from a published study. Simulation of 1,000 virtual MICs was performed using the MICs of 78 clinical isolates of S. aureus collected from a hospital in Korea. Thereafter, these simulated MICs were randomly allocated to 1,000 virtual patients in whom the TARs for AUC₂₄/MIC >125 [or 345] and C_trough >10 [or 20] mg/L were determined. The relationship of the maintenance dose with the steady-state TAR was predicted with respect to the AUC₂₄/MIC >125 [or 345] using logistic analysis.

Results

The standard dose regimen of teicoplanin showed TARs of about 70% [or 33%] and 70% [or 20%] at steady-state in cases with AUC₂₄/MIC >125 [or 345] and C_trough >10 [or 20] mg/L, respectively.

Conclusion

The current standard dose regimen was predicted to be insufficient to adequately treat S. aureus in Korean patients with neutropenic fever. To assure at least an 80% TAR in this population, dose adjustment of teicoplanin should be considered.     

Involvement of human histamine N-methyltransferase gene polymorphisms in susceptibility to atopic dermatitis in korean children

Purpose

Histamine N-methyltransferase (HNMT) catalyzes one of two major histamine metabolic pathways. Histamine is a mediator of pruritus in atopic dermatitis (AD). The aim of this study was to evaluate the association between HNMT polymorphisms and AD in children.

Methods

We genotyped 763 Korean children for allelic determinants at four polymorphic sites in the HNMT gene: -465T>C, -413C>T, 314C>T, and 939A>G. Genotyping was performed using a TaqMan fluorogenic 5'' nuclease assay. The functional effect of the 939A>G polymorphism was analyzed.

Results

Of the 763 children, 520 had eczema and 542 had atopy. Distributions of the genotype and allele frequencies of the HNMT 314C>T polymorphism were significantly associated with non-atopic eczema (P=0.004), and those of HNMT 939A>G were significantly associated with eczema in the atopy groups (P=0.048). Frequency distributions of HNMT -465T>C and -413C>T were not associated with eczema. Subjects who were AA homozygous or AG heterozygous for 939A>G showed significantly higher immunoglobulin E levels than subjects who were GG homozygous (P=0.009). In U937 cells, the variant genotype reporter construct had significantly higher mRNA stability (P<0.001) and HNMT enzyme activity (P<0.001) than the common genotype.

Conclusions

Polymorphisms in HNMT appear to confer susceptibility to AD in Korean children.     

Association Analysis Between FILIP1 Polymorphisms and Aspirin Hypersensitivity in Korean Asthmatics

Purpose

Aspirin exacerbated respiratory disease (AERD) results in a severe asthma attack after aspirin ingestion in asthmatics. The filamin A interacting protein 1 (FILIP1) may play a crucial role in AERD pathogenesis by mediating T cell activation and membrane rearrangement. We investigated the association of FILIP1 variations with AERD and the fall rate of forced expiratory volume in one second (FEV1).

Methods

A total of 34 common FILIP1 single nucleotide polymorphisms (SNPs) were genotyped in 592 Korean asthmatic subjects that included 163 AERD patients and 429 aspirin-tolerant asthma (ATA) controls.

Results

This study found that 5 SNPs (P=0.006-0.01) and 2 haplotypes (P=0.01-0.03) of FILIP1 showed nominal signals; however, corrections for the multiple testing revealed no significant associations with the development of AERD (P_corr>0.05). In addition, association analysis of the genetic variants with the fall rate of FEV1, an important diagnostic marker of AERD, revealed no significant evidence (P_corr>0.05).

Conclusions

Although further replications and functional evaluations are needed, our preliminary findings suggest that genetic variants of FILIP1 might be not associated with the onset of AERD.     

The association of SERPINE2 gene with COPD in a Chinese Han population

Purpose

Polymorphisms of several candidate genes have been studied and associated with the development of chronic obstructive pulmonary disease (COPD). One such candidate is the SERPINE2 (Serpin peptidase inhibitor, clade E member 2) gene.

Materials and Methods

To assess whether the SERPINE2 gene is associated with COPD in a Chinese Han population. Samples were collected from a Chinese Han population and analyzed for the association of single nucleotide polymor phisms (SNPs) or haplotypes of SERPINE2 gene with COPD in a case-control study. Three SNPs including rs840088 G/A in intron 1, rs1438831 A/G in 5'' upstream sequence and rs3795879 G/A in intron 3 were detected using the polymerase chain reaction (PCR)-based restriction fragment length polymorphism technique in 409 COPD subjects and 411 controls. Genotyping of the SREPINE2 polymorphisms at positions rs840088, rs1438831and rs3795879 was performed.

Results

We found that none of the rs840088G/A, rs1438831G/A and rs3795879 G/A polymorphisms were associated with the disease. The p-values were 0.630, 0.208 and 0.398 respectively.

Conclusion

Our data suggested that there was no significant association between SERPINE2 polymorphism and COPD susceptibility in the Chinese Han population.     

Association of β₂-adrenergic receptor polymorphism with work-related symptoms in workers exposed to wheat flour

Purpose

Our previous study indicated that the presence of wheat-specific IgG1 and IgG4 antibodies was associated with work-related symptoms in workers exposed to wheat flour. We performed this study to investigate the genetic polymorphisms of β₂-adrenergic receptors and wheat-specific antibodies in association with the clinical parameters of baker''s asthma.

Materials and Methods

In total, 379 subjects working in a single industrial bakery were enrolled in this study. The skin prick test was performed with common inhalant allergens and wheat flour extract. The presence of serum- specific IgE, IgG1, and IgG4 antibodies to wheat flour were determined by ELISA. Whole blood samples were obtained for genotype analysis. Subjects were genotyped with regard to five candidate single nucleotide polymorphisms (SNPs) of the β₂-adrenergic receptor gene (ADRB2; -47 T>C, 46 A>G, 79 C>G, 252 G>A, and 523 C>A) using a single-base extension method.

Results

No significant associations were observed between the genotype/allele frequencies of any of the SNPs tested and any clinical parameters. The haplotype of ADRB2 (GAA composed of 46 A>G, 252 G>A, and 523 C>A) was significantly associated with work-related symptoms (p<0.05). Moreover, in subjects with the AG or GG genotype at 46 A>G and haplotype [GAA] of ADRB2, the prevalence rates of wheat-specific IgG1 antibodies and lower respiratory symptoms increased significantly with exposure intensity (both p<0.05).

Conclusion

The findings of the present study suggest that ADRB2 genetic polymorphism may contribute to the development of work-related symptoms in workers exposed to wheat flour, which can lead to baker''s asthma.     

Association between CDH13 Variants and Cardiometabolic and Vascular Phenotypes in a Korean Population

Purpose

Although some CDH13 single nucleotide polymorphisms (SNPs) have been shown to be determinants of blood adiponectin levels, the clinical implications of CDH13 variants are not yet completely understood. The purpose of this study was to evaluate the effects of SNPs of CDH13 on metabolic and vascular phenotypes.

Materials and Methods

We included 238 hypertensive subjects and 260 age- and sex-matched controls. Seven tagging-SNPs were identified in the CDH13 gene by whole gene sequencing. The association between these SNP variants and the risk of hypertension, metabolic traits, and carotid intima-media thickness (IMT) was examined.

Results

Minor allele carriers of rs12444338 had a lower risk of hypertension, but the association turned out just marginal after adjusting confoudners. Blood glucose levels were higher in the minor allele carriers of c.1407C>T (p=0.01), whereas low-density lipoprotein-cholesterol levels were greater in those of rs6565105 (p=0.02). The minor allele of rs1048612 was associated with a higher body mass index (p=0.01). In addition, the mean carotid IMT was significantly associated with rs12444338 (p=0.02) and rs1048612 (p=0.02).

Conclusion

These results provide evidence that CDH13 variants are associated with metabolic traits and carotid atherosclerosis in Koreans. This study shows the multifaceted effects of CDH13 variants on cardiometabolic risk.     

Homozygous SMN2 deletion is a major risk factor among twenty-five Korean sporadic amyotrophic lateral sclerosis patients

Purpose

The association between survivor motor neuron (SMN) gene deletion and spinal muscular atrophy suggests that sporadic amyotrophic lateral sclerosis (sALS) may be related to SMN deletion. We examined the association between the SMN genotype and susceptibility to and severity of sALS.

Materials and Methods

We genotyped the copy number of SMN1 and SMN2 in 25 patients diagnosed with sporadic ALS and 100 healthy subjects in a Korean population. Onset age and medical research council (MRC) scale were compared among patients according to SMN1 : SMN2 genotypes.

Results

There was a significantly higher incidence of homozygous deletion of SMN2 (SMN1 : SMN2 genotype, 2 : 0) in sALS patients (20%) than in the normal controls (2%) (p<0.001). The onset age for patients with homozygous deletion of SMN2 (2 : 0) was significantly younger (34±15.38 years) than that of patients with 2 : 1, 2 : 2 and 2 : 3 of the SMN1 : SMN2 genotype (59.5±5.09; 52.69±16.46 and 50±0.00 years) (p=0.049). The ratio of patients with an MRC scale above G4- was smaller in the 2 : 0 genotype (40%) than in the 2 : 1, 2 : 2 and 2 : 3 genotypes (83.3%, 100% and 100%) (p=0.02).

Conclusion

The homozygous SMN2 deletion (2 : 0) was statistically more frequent and associated with earlier onset age and lower MRC scale in Korean sALS patients. These suggest that SMN2 deletion may be one of the factors associated with susceptibility to and severity of sALS in a Korean population.     

Trends in ischemic heart disease and stroke death ratios in brazilian women and men

OBJECTIVE:

Cardiovascular diseases are the main cause of death in women and men in Brazil, but the trends for the death ratios for ischemic heart disease and stroke in women and men remain unknown.

METHOD:

In this study, the trends for the death ratios among women and men who were over 30 years of age were analyzed from 1980 to 2005. Data were collected for both the Brazilian population and the metropolitan area of São Paulo. Estimates of the population size and data for mortality were then obtained from the Brazilian Institute of Geography and Statistics and the Ministry of Health. The risk for death was adjusted using a direct method.

RESULTS:

Death rates due to cardiovascular disease, ischemic heart disease, and stroke have declined in both Brazil and the metropolitan region of São Paulo. A linear regression analysis revealed a similar trend for ischemic heart disease and demonstrated a male/female ratio of 1.653 ± 0.001 (r = 0.228; p = 0.262) in Brazil and 1.763 ± 0.008 (r = 0.863; p<0.001) in São Paulo. Comparisons between the slopes of the linear regressions showed an increased ischemic heart disease ratio in men/women in São Paulo in comparison to those in Brazil (p<0.0001). The linear regression showed an increasing trend for the male/female stroke ratio of 1.252 ± 0.004 (r = 0.776; p<0.0001) in Brazil and 1.331 ± 0.006 (r = 0.580; p = 0.002) in São Paulo. Comparisons between the regressions for the stroke ratio were similar for men/women in São Paulo compared to Brazil (p = 0.244).

CONCLUSION:

We observed an increased trend in the ratio for ischemic heart disease death in men compared to women. Improvements in the control of risk factors and treatments for both men and women are mandatory to reduce the number of ischemic heart disease‐related deaths in Brazil.     

Does higher quality primary health care reduce stroke admissions? a national cross-sectional study

Background

Hospital admission rates for stroke are strongly associated with population factors. The supply and quality of primary care services may also affect admission rates, but there is little previous research.

Aim

To determine if the hospital admission rate for stroke is reduced by effective primary and secondary prevention in primary care.

Design and setting

National cross-sectional study in an English population (52 763 586 patients registered with 7969 general practices in 152 primary care trusts).

Method

A combination of data on hospital admissions for 2006–2009, primary healthcare staffing, practice clinical quality and access indicators, census sources, and prevalence estimates was used. The main outcome measure was indirectly standardised hospital admission rates for stroke, for each practice population.

Results

Mean (3 years) annual stroke admission rates per 100 000 population varied from zero to 476.5 at practice level. In a practice-level multivariable Poisson regression, observed stroke prevalence, deprivation, smoking prevalence, and GPs/100 000 population were all risk factors for hospital admission. Protective healthcare factors included the percentage of stroke or transient ischaemic attack patients whose last measured total cholesterol was ≤5 mmol/l (P<0.001), and ability to book an appointment with a GP (P<0.003). All effect sizes were relatively small.

Conclusion

Associations of stroke admission rates with deprivation and smoking highlight the need for smoking-cessation services. Of the stroke and hypertension clinical quality indicators examined, only reaching a total cholesterol target was associated with reduced admission rates. Patient experience of access to primary care may also be clinically important. In countries with well-developed primary healthcare systems, the potential to reduce hospital admissions by further improving the clinical quality of primary healthcare may be limited.     

Clinical and Pathological Heterogeneity of Korean Patients with CAPN3 Mutations

Purpose

This study was designed to investigate the characteristics of Korean patients with calpainopathy.

Materials and Methods

Thirteen patients from ten unrelated families were diagnosed with calpainopathy via direct or targeted sequencing of the CAPN3 gene. Clinical, mutational, and pathological spectra were then analyzed.

Results

Nine different mutations, including four novel mutations ({"type":"entrez-nucleotide","attrs":{"text":"NM_000070","term_id":"27765081","term_text":"NM_000070"}}NM_000070: c.1524+1G>T, c.1789_1790inA, c.2184+1G>T, and c.2384C>T) were identified. The median age at symptom onset was 22 (interquartile range: 15-28). Common clinical findings were joint contracture in nine patients, winged scapula in four, and lordosis in one. However, we also found highly variable clinical features including early onset joint contractures, asymptomatic hyperCKemia, and heterogeneous clinical severity in three members of the same family. Four of nine muscle specimens revealed lobulated fibers, but three showed normal skeletal muscle histology.

Conclusion

We identified four novel CAPN3 mutations and demonstrated clinical and pathological heterogeneity in Korean patients with calpainopathy.     

The ADA*2 allele of the adenosine deaminase gene (20q13.11) and recurrent spontaneous abortions: an age-dependent association

OBJECTIVE:

Adenosine deaminase acts on adenosine and deoxyadenosine metabolism and modulates the immune response. The adenosine deaminase G22A polymorphism (20q.11.33) influences the level of adenosine deaminase enzyme expression, which seems to play a key role in maintaining pregnancy. The adenosine deaminase 2 phenotype has been associated with a protective effect against recurrent spontaneous abortions in European Caucasian women. The aim of this study was to investigate whether the G22A polymorphism of the adenosine deaminase gene is associated with recurrent spontaneous abortions in Brazilian women.

METHODS:

A total of 311 women were recruited to form two groups: G1, with a history of recurrent spontaneous abortions (N = 129), and G2, without a history of abortions (N = 182). Genomic DNA was extracted from peripheral blood with a commercial kit and PCR-RFLP analysis was used to identify the G22A genetic polymorphism. Fisher''s exact test and odds ratio values were used to compare the proportions of adenosine deaminase genotypes and alleles between women with and without a history of recurrent spontaneous abortion (p<0.05). The differences between mean values for categorical data were calculated using unpaired t tests. The Hardy-Weinberg equilibrium was assessed with a chi-square test.

RESULTS:

Statistically significant differences were identified for the frequencies of adenosine deaminase genotypes and alleles between the G1 and G2 groups when adjusted for maternal age.

CONCLUSIONS:

The results suggest that the adenosine deaminase *2 allele is associated with a low risk for recurrent spontaneous abortions, but this association is dependent on older age.     

Probable role of Beta 2-adrenergic receptor gene haplotype in toluene diisocyanate-induced asthma

Purpose

A genetic polymorphism of the beta 2-adrenergic receptor is a major factor associated with the asthmatic phenotype. The association of this polymorphism with toluene diisocyanate (TDI)-induced asthma has not been investigated. We examined 103 TDI-induced asthma patients (TDI-OA), 60 asymptomatic exposed controls (AEC), and 263 unexposed healthy controls (NC) in order to identify beta 2-adrenergic receptor gene (ADRB2) polymorphisms and the possible association with TDI-induced asthma.

Methods

Single nucleotide polymorphisms (SNPs) of ADRB2 were genotyped by direct sequencing. Serum-specific IgE and IgG levels were measured using an enzyme-linked immunosorbent assay. Phenotypes and clinical patient parameters were compared.

Results

SNPs were identified (-47 T>C, -20 T>C, Arg16Gly A>G, Gln27Glu C>G, Leu134Leu G>A, Arg175Arg C>A) during ADRB2 screening (from -231 to 793 bp). No significant differences in allelic and genotypic frequencies were noted for any of the six ADRB2 SNPs. The Arg16Gly A>G, Leu134Leu G>A, and Arg175Arg C>A SNPs and haplotype 1 [TTACGC] were significantly associated with specific IgE antibodies to the TDI-human serum albumin (HSA) conjugate in TDI-exposed subjects (P<0.05). Exposed workers with the ADRB2 ht1/ht1 homozygote had a significantly higher TDI-HSA conjugate-specific IgE sensitization rate than did those with the null ht1 haplotype (odds ratio, 15.40; 95% confidence interval, 1.81-131.06).

Conclusions

ADRB2 polymorphisms may affect IgE-specific sensitization to TDI-HSA conjugate in TDI-exposed workers.     

Molecular and Epidemiological Characterization of Carbapenem-Resistant Acinetobacter baumannii in Non-Tertiary Korean Hospitals

Purpose

The increasing prevalence and global spread of carbapenem-resistant Acinetobacter baumannii (A. baumannii) has become a serious problem. The aim of this study was to investigate molecular and epidemiological characteristics of carbapenem-resistant A. baumannii isolates collected from Korean non-tertiary hospitals.

Materials and Methods

Thirty six non-duplicated carbapenem-resistant A. baumannii isolates were collected from 17 non-tertiary hospitals in Korea between 2004 and 2006. Isolates were typed by multilocus sequence typing and repetitive-sequence-based PCR (rep-PCR). Detection of genes encoding OXA carbapenemase and their relationship with ISAba1 was performed by PCR.

Results

Two clones were prevalent among 36 isolates: ST69 (17 isolates, 47.2%) and ST92 (19 isolates, 52.8%). Rep-PCR patterns were diverse and revealed that all isolates were clustered into eight band patterns. The ISAba1-activated blaOXA-23-like and ISAba1-activated blaOXA-51-like genes were prevalent among the carbapenem-resistant A. baumannii isolates.

Conclusion

The class D β-lactamase genes of A. baumannii were distributed nationwide in non-tertiary Korean hospitals.     

In-vitro antimicrobial activity of selected honeys on clinical isolates of Helicobacter pylori

Background

Helicobacter pylori is a gram-negative bacterium incriminated in gastroduodenal ulcers, and mucosa-associated lymphoid tissue lymphoma imposing a major burden on health care systems worldwide. Honeys have been shown to have in vitro activity against microaorganisms and suitable for use in ulcers, infected wounds and burns.

Objective

The study was aimed at evaluating the antimicrobial potential of honeys (Manuka−, Capillano®, Eco- and Mountain) at different concentrations (10%v/v, 20%v/v, 50%v/v and 75%v/v) against clinical isolates of H. pylori.

Methods

H. pylori was isolated from gastric biopsies of patients with gastroduodenal pathologies following standard microbiological procedures. Antimicrobial susceptibility of the isolates to different honey varieties was determined by the disk diffusion assay. Also, the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of the most potent honey was determined by the agar dilution method. Data were analysed using the Fisher exact test and statistical significance considered at p<0.05.

Results

All the four honey varieties exhibited antibacterial activity. The strongest inhibitory activity (82.22%) was demonstrated by Mountain honey at 75%v/v, followed by Capillano® and Manuka− honeys (75.56%), and Eco-honey (73.36%) at the same concentration. However, no statistically significant difference (p>0.05) was noted between the honeys at different concentrations. The MIC and MBC concentrations of Mountain honey were in the range 0.117 – 0.938ì/mL and 0.366 – 2.965ìg/mL respectively. The antimicrobial potential of these honeys at different concentrations were highly comparable to clarithromycin, the positive control.

Conclusion

These honeys may contain compounds with therapeutic potential against our local isolates of H. pylori.     

The Relationship between Gastric Juice Nitrate/Nitrite Concentrations and Gastric Mucosal Surface pH

Purpose

To investigate gastric juice nitrate/nitrite concentration according to mucosal surface pH extent (area) of gastric corpus intimately contacting the gastric juice.

Materials and Methods

We included ninety-nine patients with dyspepsia. To evaluate gastric mucosal surface pH and its extent, gastric chromosocpy was performed by spraying phenol red dye on the corpus mucosa and estimating the extent of area with color changed. Nitrate/nitrite concentrations and pH of gastric juice were measured by ELISA and pH meter, respectively. Silver staining was done to histologically confirm the presence of Helicobacter pylori.

Results

Intragastric nitrate/nitrite concentrations in patients, showing phenol red staining mucosa were higher than those of unstaining mucosa (p=0.001): the more extensive in the area of phenol red staining area of corpus, the higher gastric juice pH found (r=0.692, p<0.001). Furthermore, the intragastric nitrate/nitrite concentrations correlated positively with gastric juice pH (r=0.481, p<0.001).

Conclusion

The changes of mucosal surface pH and its extent in gastric corpus might affect either pH or nitrate/nitrite level of gastric juice.     

No associations of human pulmonary tuberculosis with Sp110 variants

Background

After a recent report on the role of the Ipr1 gene in mediating innate immunity in a mouse model of Mycobacterium tuberculosis infection, the human Ipr1 homologue, Sp110, was considered a promising candidate for an association study in human tuberculosis.

Methods

In a sample of >1000 sputum positive, HIV negative West African patients with pulmonary tuberculosis and >1000 exposed, apparently healthy controls, we have genotyped 21 Sp110 gene variants that were either available from public databases, including HapMap data, or identified by DNA re‐sequencing.

Results

No significant differences in the frequencies of any of the 21 variants were observed between patients and controls. This applied also for HapMap tagging variants and the corresponding haplotypes, when including sliding window analyses with three adjacent variants, and when stratifying controls for positivity and negativity according to the results of intradermal tuberculin (purified protein derivative, PPD) skin tests. DNA re‐sequencing revealed 13 novel Sp110 variants in the 5′‐UTR, exons, and adjacent intronic regions.

Conclusions

Based on the results obtained in this case‐control study, the hypothesis that Sp110 variants and haplotypes might be associated with distinct phenotypes of human M tuberculosis infection is doubtful.     

The effect of Nigella sativa extract on tracheal responsiveness and lung inflammation in ovalbumin-sensitized guinea pigs

OBJECTIVE:

To examine the preventive effect of a hydro-ethanolic extract of Nigella sativa on the tracheal responsiveness and white blood cell count in the lung lavage fluid of sensitized guinea pigs.

METHODS:

Three groups of guinea pigs sensitized to intraperitoneally injected and inhaled ovalbumin were given drinking water alone (group S), drinking water containing a low concentration of N. sativa extract (group S+LNS) or drinking water containing a high concentration of N. sativa extract (group S+HNS). The tracheal responses of control animals (group C) and the three groups of sensitized guinea pigs (n = 7 for all groups) to methacholine were measured by the assessment of the tracheal smooth muscle response to increasing concentrations of methacholine, and the effective concentration causing 50% of the maximum response (EC₅₀) was determined. Tracheal responses to 0.1% ovalbumin and white blood cell counts in the lung lavage fluid were also examined.

RESULTS:

The tracheal response of the group S guinea pigs to both methacholine and ovalbumin was significantly higher than the response of the controls (p<0.01 for both cases). The tracheal responses of the S+LNS and S+HNS groups to both methacholine and ovalbumin were significantly decreased compared to those of the S group (p<0.05 to p<0.01). The total white blood cell and eosinophil counts in the lung lavage fluid of group S were significantly higher than those of group C (p<0.01). The white blood cell counts in both treated groups showed significant improvements (p<0.01 for both cases).

CONCLUSIONS:

These results demonstrate the preventive effect of the N. sativa extract on the tracheal response and lung inflammation in sensitized guinea pigs.     

Role of Toll-like Receptor 3 Variants in Aspirin-Exacerbated Respiratory Disease

Purpose

Although the mechanism of virus-induced, aspirin-exacerbated respiratory disease (AERD) is not known fully, direct activation of viral components through Toll-like receptor 3 (TLR3) has been suggested. TLR3 recognizes double-stranded RNA (dsRNA), and activates nuclear factor-κB and increases interferon-γ, which signals other cells to induce airway inflammation in asthma. Considering the association of TLR3 in viral infections and AERD, we investigated whether promoter and non-synonymous variants of TLR3 were associated with AERD.

Methods

The three study groups, 203 with AERD, 254 with aspirin-tolerant asthma (ATA), and 274 normal healthy controls (NC) were recruited from Ajou University Hospital, Korea. Two polymorphisms, -299698G>T and 293391G>A [Leu412Phe], were genotyped using primer extension methods.

Results

Genetic associations were examined between two genetic polymorphisms of TLR3 (-299698G>T and 293391G>A [Leu412Phe]) in the three study groups. AERD patients that carried the GG genotype of 293391G>A showed a significantly lower frequency compared with ATA in both co-dominant (P=0.025) and dominant models (P=0.036). Similarly, in the minor allele frequency, the A allele was significantly higher (P=0.023) in AERD compared with ATA for this polymorphism. AERD patients who carried HT2 [GA] showed a significantly higher frequency than other haplotypes in co-dominant (P=0.02) and recessive (P=0.026) models.

Conclusions

Our findings suggest that the -299698G>T and 293391G>A [Leu412Phe] polymorphisms of the TLR3 gene are associated with the AERD phenotype.     

Antidiabetic and haematinic effects of Parquetina nigrescens on alloxan induced type-1 diabetes and normocytic normochromic anaemia in Wistar rats

Background

The plant, Parquetina nigrescens is used in folklore medicine to treat diabetes mellitus and its complications in several parts of West Africa.

Objective

To determine the effect of Parquetina nigrescens extract on fasting blood glucose in alloxan-induced diabetic rats.

Methods

The blood glucose levels, complete blood count, erythrocyte indices and osmotic fragility, body and organ weights were evaluated.

Results

Diabetic rats treated with the extract showed significant (P<0.01) reduction of the blood glucose to levels comparable to that of the non-diabetic control and those treated with chlorpropamide (standard drug). Similarly, there was significant (P<0.01) reduction in the complete blood count in the diabetic rats.

Discussion

The anaemia, leucopenia and thrombocytopenia associated with the diabetes were corrected in the animals treated with the extract and chlorpropamide. The extract also reduced the erythrocyte osmotic fragility, body and organ weights. Parquetina nigrescens demonstrated antidiabetic property by reducing the elevated blood glucose in alloxan treated rats which is comparable to animals that received the standard drug.

Conclusion

Paraquetina nigrescens stabilized the erythrocyte membrane, decreased the body weight probably by lowering lipogenesis. However, the mechanism underlying the antidiabetic and haematinic properties of Parquetina nigrescens remains to be elucidated.